Joshua Ferris’sThen We Came to the End was one of the most socially intricate and comically astute first novels of recent years. It used an unusual first-person plural point of view to represent individuality-muffling work in a large Chicago ad agency. Only a woman dying of cancer escapes the “we” or, more precisely, has singularity imposed upon her by her illness. Densely populated, fine-grained, and large-hearted, Then We Came to the End won the PEN/Hemingway Award for First Fiction and the Barnes & Noble Discover Award, and was a National Book Award finalist in 2007.

In The Unnamed Ferris places disease at the book’s center, where it defines character, controls the narrative, and even dictates this second novel’s settings. Tim Farnsworth, a successful Manhattan litigator, finds himself suddenly compelled to walk — out of his office, out of conversations, away from home. He can’t anticipate an onset, can’t choose where the walk will take him, stops only when exhausted, sleeps outdoors wherever he stops, and calls his wife to come get him when he wakes. His compulsion makes him an inattentive father to his teenage daughter, Becka; deprives him of his job; eventually separates him from his beloved wife, Jane; causes him to lose toes and fingers to frostbite; and finally consigns him to wandering the American continent.

Although Ferris never names his protagonist’s literal dis-ease, his book joins a group of recent “syndrome novels”: Richard Powers’s The Echo Maker (Capgras syndrome), Mark Haddon’s The Curious Incident of the Dog in the Night-Time (Asperger’s), Ian McEwan’s Enduring Love (de Clerambault’s), and Jonathan Lethem’s Motherless Brooklyn (Tourette’s). The danger for fiction from what might be called the Oliver Sacks syndrome (he is alluded to in The Echo Maker and in The Unnamed) is a novel’s becoming an exercise in exotic pathology. Powers avoids this by concentrating on the variously motivated characters responding to the Capgras sufferer. Ferris courts the danger and ups the ante by intensely focusing on his walker, a choice that ultimately transforms pathology into a gouging existential metaphor. As Faulkner said, life is motion. The need for movement pervades many American novels, including Updike’s Rabbit Run and DeLillo’s Running Dog, but Ferris’s compulsive pedestrian pushes beyond these runners’ urges to a primal truth.

Move or die.

Before recognizing this grim choice at novel’s end, readers will find plenty of sunnier fictional pleasures. Tim’s work at the law firm yields amusing anecdotes about other obsessive attorneys who manage to keep or improve their positions. Becka, who suffers from an eating disorder, changes from a resentful teenage caretaker of her father to an independent spirit and then to a sympathetic, if brief, caretaker. Living with Tim drives his wife to drive (to chain restaurants in Connecticut) and to drink, but Jane reclaims herself and attempts to regain Tim as he roams farther and farther away. Ferris also inserts a murder mystery that Tim might have solved had he not been in the throes of his syndrome.

But the novel is fundamentally and increasingly about Tim. Trained in linguistic precision, legal precedent, and observable causality, he assumed at the first onset that some doctor — even if it’s only “the One Guy” — would be able to name and explain, if not cure, his condition. Tim’s worldwide search for that “One Guy” lightens flashbacks with cameos by several obviously crank healers. In the novel’s present — twelve years after the initial onset, eight years after a relapse during which Tim was handcuffed to his bed for 27 months, and four years after Tim and Jane fled their suburban home — Tim decides to leave his wife (for her own good), let his walks take him where they will, and war against himself alone.

Ferris records arguments between mind, which Tim clings to as self, and body, which Tim assumes is causing the compulsion because, rational materialist that he is, he discounts psychological causation. Physically weakened by his random walk across America, Tim desperately enlists God’s help to turn self into soul and gain an edge over body. Enforced hospitalizations and antipsychotic drugs help restore his rationality — but also the body that just keeps walking. Tim refuses to accept that some aspect of the mind is inviolate to legal analysis or that the body’s brain may be commanding his legs. This obduracy is his heroism but also his hubris and leads to the “lesson” of syndrome novels: that the body/brain interface — what the neuroscientists call “embodiment” — is more enigmatic than lawyers can imagine and even scientists explain. Or to quote Emily Dickinson, whose “After Great Pain” supplies titles for the novel’s four parts, “the brain is wider than the sky.”

Ferris’s brain falters a bit in the last third of the novel, when Tim gets as far west as Portland. Settings are fleetingly registered through Tim’s consciousness, which is mostly busy with its mind/body combat. Although the resulting fragmentation is appropriate, it’s also repetitive and opaque. Perhaps to reward the reader for accompanying a disintegrating consciousness and disfigured body across a mostly disheartening landscape, Ferris allows Tim to briefly overcome his compulsion for a rather unlikely and therefore sentimental family reunion near the novel’s end.

Once the pathological mainspring of The Unnamed is accepted, it’s a consistently realistic book. It can even be read as a moving account of homelessness (though Tim always has plenty of money). But the novel is also a textual syndrome, the place (from the Greek) where other fictions “run together.” Ferris’s numerous descriptions of nature as a “freak menace” and the plot’s determinism hark back to the naturalists, to novels such as Norris’s McTeague and Dreiser’s Sister Carrie, which incorporated the skull and brain science of their time. Since Ferris took the title of his first novel from DeLillo’s Americana, The Unnamed can’t help but recall DeLillo’s The Names, in which a name-searching wanderer ends as Tim does. But the most important precursor is Beckett’s The Unnameable, which Ferris has identified as one of his favorite novels. Beckett’s self-splintering protagonist can’t move. Ferris’s schizoid character can’t stop. Beckett’s narrator says, “I can’t go on, I’ll go on.” Tim’s mind says to his body, “You go on and on.” The Unnamed stops, but its story of a kinked mind and its intersections with other fictions go on and on in the reader’s mind.

Then We Came to the End explored with great vigor the horizontal “x” axis of social, cultural, and economic relationships. The Unnamed obsessively tunnels down the “y” axis of self to arrive at another meaning of “x” the unknown. Taken together, the novels demonstrate a wide-ranging and deep-plunging new talent at work.